Biological controls for microbials are diminishing as societies construct more confined dwelling spaces. Fungi are one of the most prevalent life forms in nature and are a highly competitive and hardy species. Recent climatic events, such as torrential storms and flooding, have caused severe fungal emergencies that pose risks for human health in many parts of the world. Additionally, construction materials such as wood and paper are ideal food sources for various fungi, some of which are extremely hazardous to human health and may be primary carriers of fungal growths.
Fungicidal action typically occurs as an inhibition of spore germination and/or inhibition of fungus growth. Physiologically, fungicides are normally metabolic inhibitors of electron transport chains, enzymes, nucleic acid metabolism, or protein synthesis, or inhibitors of sterol synthesis. Most of the fungicidal chemicals acting through such modes of toxicity have negative effects on human health, unlike propionic acid and its salts. Therefore, there is a need for an effective fungicide posing low human health risks with immediate and residual toxicity to fungi where infestations may occur.
Propionic acid and its salts are used as a food additive to inhibit microbial growth in breads, cheeses, confections, doughs, puddings, jams and jellies, fresh dough, and meat products. As a food additive, propionic acid and propionic acid salts are designated as generally recognized as safe, or GRAS, by the FDA. Propionic acid has also been used as an antimicrobial inhibitor and preservative in pharmaceuticals, tobacco, cosmetics, animal feeds, and harvested grains and seeds.
Propionic acid occurs naturally in animals (including humans) and dairy products. In animals it is a normal intermediary metabolite that is metabolized to glucose, carbohydrates, amino acids, and lipids, in the same manner as fatty acids (see http://www.nysaes.cornell.edu/fst/fvc/Venture/venture3_chemical.html). Chemically, propionic acid and its salts have a monobasic carboxylic acid structure and its mode of inhibition action on microbials is reportedly due to blockage of acetate in the acetokinase systems, interference with B-alanine in pantothenic acid synthesis, and blockage of pyruvate conversion to acetyl-coenzyme A (Bassler, Anthony: Am J Gastroenterol. 1959 December; 32: 757-70). Medicinally, propionate compounds are typically used as either internal or topical antifungal agents (American Hospital Formulary Service. Volumes I and II. Washington, D.C.: American Society of Hospital Pharmacists, to 1984, p. 84:04).
Historically, the use of propionic acid and its salts as antifungal agents, has had the inherent disadvantage of a relatively short-lived effectiveness. For example, in most food applications the efficacy is reportedly limited to about eight days (Furia, T. E. (Ed.). CRC Handbook of Food Additives. 2nd Ed. Cleveland: The Chemical Rubber Co., 1972. p. 139). Despite the short term effectiveness, the low acute and long term health risks coupled with a relatively safe environmental impact makes propionic acid and its salts an attractive ingredient for use as an antifungal inhibitor in some applications. In spite of these attractive qualities, the use of propionate compounds in commercial and industrial applications has been much less common because the concentrations required for acceptable efficacy levels would be considered a human health risk.
Therefore, a need exists for propionate compounds having increased efficacy as a fungicide without increasing human health risks.